MAIT cells are imprinted by the microbiota in early life and promote tissue repair.

MAIT cells are imprinted by the microbiota in early life and promote tissue repair.
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DOI:
10.1126/science.aax6624
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发表时间:
2019-10-25
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Belkaid Y
Belkaid Y
中科院分区:
其他
文献类型:
--
作者:
Constantinides MG;Link VM;Tamoutounour S;Wong AC;Perez-Chaparro PJ;Han SJ;Chen YE;Li K;Farhat S;Weckel A;Krishnamurthy SR;Vujkovic-Cvijin I;Linehan JL;Bouladoux N;Merrill ED;Roy S;Cua DJ;Adams EJ;Bhandoola A;Scharschmidt TC;Aubé J;Fischbach MA;Belkaid Y

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早期的定居和随后暴露在微生物区系中如何影响长期的组织免疫仍然知之甚少。在这里,我们表明,粘膜相关不变T细胞(MAIT)的发育依赖于特定的时间窗口,在此之后,MAIT细胞的发育受到永久性的损害。这种印记依赖于生命早期接触到合成核黄素衍生抗原的特定微生物。在成人中,皮肤MAIT细胞是产生IL-17A的淋巴细胞的主要群体,这些淋巴细胞显示出独特的转录信号,随后能够以IL-1、IL-18和抗原依赖的方式对皮肤共生作出反应。因此,皮肤MAIT细胞的局部激活促进了伤口的愈合。总而言之,我们的工作揭示了微生物区系的特定成员和MAIT细胞之间的特权相互作用,这种作用顺序地控制着组织印记和随后对伤害的反应。早期的微生物暴露印记了大量与粘膜相关的不变T细胞,随后与微生物区系的相互作用调节了它们促进组织修复的能力。
How early-life colonization and subsequent exposure to the microbiota impact long-term tissue immunity remains poorly understood. Here we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of IL-17A-producing lymphocytes, which display a unique transcriptional signature and can subsequently respond to skin commensals in an IL-1-, IL-18-, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury. Early-life microbial exposure imprints the abundance of mucosal-associated invariant T cells and subsequent interactions with the microbiota modulate their ability to promote tissue repair.
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